Association between genomic instability score and progression-free/overall survival in patients with newly diagnosed non-BRCA1/2 ovarian cancer Journal Article
| Authors: | Graves, S.; Sullivan, M. W.; Adkoli, A.; Zhou, Q.; Iasonos, A.; Selenica, P.; Aghajanian, C.; Liu, Y. L.; Tew, W.; Sonoda, Y.; Ellenson, L. H.; Chi, D.; O'Cearbhaill, R. E.; Weigelt, B.; Grisham, R. N. |
| Article Title: | Association between genomic instability score and progression-free/overall survival in patients with newly diagnosed non-BRCA1/2 ovarian cancer |
| Abstract: | Objective: We sought to describe the association between genomic instability score (GIS) and progression-free survival (PFS) and overall survival (OS) in patients with newly diagnosed, non-BRCA1/2 ovarian cancer. Methods: Homologous recombinant deficiency (HRD) status was based on a cutoff of ≥42 GIS; patients <42 were categorized with homologous recombination proficiency (HRP). We collected type and duration of maintenance therapy, among other variables, and built a multivariate model with landmark analysis at 6 months from baseline and applied it for time-dependent variables. Results: Increasing GIS as a continuous variable was associated with improved PFS and OS in our cohort. Overall, median PFS was significantly longer in patients with HRD ovarian cancer (35.4 months, 25.4–NE) than in those with HRP disease (14.9 months, 13.1–16.2; p < 0.001). Median OS was 36.2 months (32.4–NE) for HRP and not reached for HRD (p = 0.002). Notably, in patients with HRP ovarian cancer, we observed a shorter median PFS in those who received a poly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi) than in those who did not (12.7 months for HRP with PARPi vs 15.2 months for HRP without PARPi). Conclusions: Our results demonstrate that in newly diagnosed advanced non-BRCA1/2 ovarian cancer, GIS as a continuous variable is associated with longer PFS and OS. In patients with HRP ovarian cancer, PARPi treatment may be associated with shorter PFS, which warrants further evaluation. © 2024 Elsevier Inc. |
| Keywords: | adult; controlled study; human tissue; aged; major clinical study; overall survival; somatic mutation; bevacizumab; cancer combination chemotherapy; paclitaxel; cancer patient; cancer diagnosis; ovarian cancer; homologous recombination; carboplatin; progression free survival; maintenance therapy; cohort analysis; brca1 protein; brca2 protein; medical record review; retrospective study; cancer hormone therapy; cancer center; dna; genomic instability; scoring system; ovary carcinoma; multivariate analysis; genetic screening; olaparib; germline mutation; parp inhibitor; niraparib; rucaparib; very elderly; human; female; article; brca-negative homologous recombination deficiency outcomes; homologous recombination deficiency testing; genomic instability score; homologous recombinant deficiency |
| Journal Title: | Gynecologic Oncology |
| Volume: | 192 |
| ISSN: | 10956859 |
| Publisher: | Elsevier B.V. |
| Date Published: | 2025-01-01 |
| Start Page: | 120 |
| End Page: | 127 |
| Language: | English |
| DOI: | 10.1016/j.ygyno.2024.11.011 |
| PROVIDER: | scopus |
| PUBMED: | 39647188 |
| PMCID: | PMC11761360 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledge in the PDF -- Corresponding authors is MSK author: Rachel N. Grisham -- Source: Scopus |
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